1. Field of the Invention
The present invention relates to pharmaceutical compositions comprising triprolidine, and more particularly to tablets containing triprolidine hydrochloride and processes for producing and assaying such tablets.
2. Background of the Invention
Triprolidine hydrochloride monohydrate is a monograph/compendial antihistamine contained in a variety of pharmaceutical products. The compound and methods for producing it are disclosed by Adamson in U.S. Pat. Nos. 2,712,020 and 2,712,023 and by Adamson et al., J. Chem. Soc. 312 (1958). A more recent publication describing triprolidine and methods for producing it is Analytical Profiles of Drug Substances, Vol. 8, pp. 509-528 (Florey, Ed., Academic Press, N.Y., 1979).
Triprolidine demonstrates unusual behavior when used in certain pharmaceutical preparations. Due to its low dose and to insure content uniformity, triprolidine is normally wet processed with standard pharmaceutical excipients, then dried and tableted. The commonly used excipients are starches, sugars and celluloses. The formulations prior to tableting contain the expected level of triprolidine with good content uniformity.
However, when the tablets are evaluated using the required United States Pharmacopeia dissolution assays (United States Pharmacopeia 23/The National Formulary 18, pp. 1606-1608 (1994)), only 85% to 90% of the triprolidine appears to dissolve. This behavior is noted even though all of the individual components of the tablet are extremely water soluble. This type of dissolution has even been observed with simple triprolidine granulations prior to compressing them into a tablet. In the past, this 85%-90% release level was largely acceptable because the USP dissolution S-1 acceptance criterion (i.e., tolerance) was 80%. However, as USP is raising the minimum tolerance level to 85%, batches formally considered acceptable will now be borderline at best.
Thus, a need exists to improve the performance of triprolidine compositions in USP testing. A need also exists to improve the availability of triprolidine hydrochloride in tablets prepared by, e.g., wet granulation or direct compression, and tested according to USP standards.
All references cited herein are incorporated by reference herein in their entireties.